Safety findings from the phase 3 FLAURA2 trial appear to be consistent with the known profiles of osimertinib and chemotherapy for the treatment of those with EGFR-mutated non–small cell lung cancer.
Treatment with osimertinib (Tagrisso) in combination with chemotherapy produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with osimertinib alone in those with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC), according to a press release on data from the phase 3 FLAURA2 trial (NCT04035486).
The treatment discontinuation rate due to adverse effects (AEs) and overall safety profile of osimertinib plus chemotherapy were consistent with previous reports of each agent. Data for overall survival (OS) were immature at the time of the analysis, which investigators plan to evaluate at a subsequent analysis.
Investigators plan to present detailed results from the FLAURA2 trial at a future medical meeting, and will share findings with global health authorities.
“As the global standard of care for EGFR-mutated [NSCLC], osimertinib monotherapy has transformed the treatment landscape, allowing many patients the opportunity to achieve improved survival,” lead investigator Pasi A. Jänne, MD, PhD, director of Lowe Cancer for Thoracic Oncology, Belfer Center for Applied Cancer Science, and Chen-Huang Center for EGFR Mutant Lung Cancers at Dana-Farber Cancer Institute and a professor of Medicine at Harvard Medical School, said in the press release.
“FLAURA2 provides compelling evidence that the addition of chemotherapy to osimertinib can provide a new option for patients and clinicians that further improves outcomes compared to osimertinib alone and, as such, can further delay treatment resistance and disease progression.”
Investigators of the open-label, multi-center, global, randomized phase 3 FLAURA assessed osimertinib with or without chemotherapy as a first-line treatment for 586 patients with locally advanced or metastatic EGFR-mutated NSCLC. Patients received 80 mg of osimertinib orally once a day with or without 500 mg/m2 of pemetrexed plus 75 mg/m2 of cisplatin or carboplatin at an area under the curve of 5 every 3 weeks for 4 cycles followed by osimertinib and pemetrexed maintenance every 3 weeks.
Patients received treatment in more than 150 centers across more than 20 countries, which included the United States and other countries in Europe, South America, and Asia.
The primary end point was PFS based on RECIST v1.1 criteria. Secondary end points included OS, objective response rate, duration of response, depth of response, disease control rate, the plasma concentration of osimertinib, and health-related quality of life.
Patients 18 years and older with pathologically confirmed nonsquamous stage IIIb, IIIc, IVa, or IVb NSCLC were eligible for enrollment on the FLAURA2 trial. Additional eligibility criteria included having tumors harboring EGFR mutations, untreated advanced disease not amenable to curative surgery or radiotherapy, a World Health Organization performance status of 0 or 1, and a life expectancy of more than 12 weeks at day 1 of treatment.
Patients who had spinal cord compression, unstable brain metastases, or a history of interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had any evidence of severe or uncontrolled systemic diseases, inadequate bone marrow reserve or organ function, refractory nausea and vomiting, or prior treatment with any systemic anti-cancer therapy for advanced NSCLC.
Receiving prior treatment with tyrosine kinase inhibitors targeting EGFR or major surgery within 4 weeks of the first dose of study treatment were also grounds for exclusion.
Tagrisso plus chemotherapy demonstrated strong improvement in progression-free survival for patients with EGFR-mutated advanced lung cancer in FLAURA2 phase III trial. News release. AstraZeneca. May 17, 2023. Accessed May 17, 2023. bit.ly/3pPq5aN